Differences in Player Performance and Longevity After Achilles Tendon Rupture Between Professional Basketball Players in the NBA and WNBA.

Background: Prior studies in the National Basketball Association (NBA) and Women's National Basketball Association (WNBA) reported worse player performance after Achilles tendon rupture (ATR). Purpose/Hypothesis: The purpose of this study was to compare time to return to play (RTP) and performance after ATR between NBA and WNBA athletes. It was hypothesized that there would be no relative difference between the NBA and WNBA players. Study Design: Cohort study; Level of evidence, 3. Methods: ATRs in the NBA between 1987 and 2017 and WNBA between 2006 and 2017 were identified through a rigorous online search of articles. Included athletes had no prior leg injuries and had played ≥3 seasons before and after ATR. Sex, age, position, body mass index, height, years of experience, time to RTP, and player efficiency rating (PER) were recorded. Relative performance was measured by matching injured athletes to uninjured controls in the same league in a 1:2 ratio. Relative differences were compared between leagues, with adjustment for baseline features. Multiple regression analysis was employed to identify variables correlating with RTP and PER. Results: Included were 102 professional basketball players, of whom 34 sustained ATR (21 male, 13 female). Sex/league correlated with differences in RTP (P < .001). There was a significant difference between the WNBA and NBA in PER when comparing 1 year pre- and 1 year postinjury (1.49 ± 0.25 vs 3.87 ± 0.43, respectively; mean ± SD P < .001). Compared with intraleague controls, the relative difference in PER postinjury was 0.81 ± 0.11 (WNBA) and 3.9 ± 0.89 (NBA) (P < .001). Multiple regression analysis indicated that when controlling for years of experience, player position, and age, NBA players took 126 days longer than WNBA players to RTP (P < .001) and NBA players had 9.96 times increased odds of taking >200 days to RTP compared with WNBA players (P = .006). Conclusion: Sex/league was a significant predictor of RTP after ATR. When compared with their respective controls, NBA players saw a greater decrease in postinjury performance than WNBA players. NBA players took longer to RTP than WNBA players. ATRs appear to more negatively affect NBA players than WNBA players.

Inflammation and heterogeneity in synucleinopathies.

Neurodegenerative diseases represent a huge healthcare challenge which is predicted to increase with an aging population. Synucleinopathies, including Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), present complex challenges in understanding their onset and progression. They are characterized by the abnormal aggregation of α-synuclein in the brain leading to neurodegeneration. Accumulating evidence supports the existence of distinct subtypes based on the site of α-synuclein aggregation initiation, genetics, and, more recently, neuroinflammation. Mediated by both central nervous system-resident cells, peripheral immune cells, and gut dysbiosis, neuroinflammation appears as a key process in the onset and progression of neuronal loss. Sex-based differences add another layer of complexity to synucleinopathies, influencing disease prevalence - with a known higher incidence of PD in males compared to females - as well as phenotype and immune responses. Biological sex affects neuroinflammatory pathways and the immune response, suggesting the need for sex-specific therapeutic strategies and biomarker identification. Here, we review the heterogeneity of synucleinopathies, describing the etiology, the mechanisms by which the inflammatory processes contribute to the pathology, and the consideration of sex-based differences to highlight the need for personalized therapeutics.

MetaFun: unveiling sex-based differences in multiple transcriptomic studies through comprehensive functional meta-analysis.

BACKGROUND: While sex-based differences in various health scenarios have been thoroughly acknowledged in the literature, we lack sufficient tools and methods that allow for an in-depth analysis of sex as a variable in biomedical research. To fill this knowledge gap, we created MetaFun as an easy-to-use web-based tool to meta-analyze multiple transcriptomic datasets with a sex-based perspective to gain major statistical power and biological soundness. DESCRIPTION: MetaFun is a complete suite that allows the analysis of transcriptomics data and the exploration of the results at all levels, performing single-dataset exploratory analysis, differential gene expression, gene set functional enrichment, and finally, combining results in a functional meta-analysis. Which biological processes, molecular functions or cellular components are altered in a common pattern in different transcriptomic studies when comparing male and female patients? This and other biological questions of interest can be answered with the use of MetaFun. This tool is available at https://bioinfo.cipf.es/metafun while additional help can be found at https://gitlab.com/ubb-cipf/metafunweb/-/wikis/Summary . CONCLUSIONS: Overall, Metafun is the first open-access web-based tool to identify consensus biological functions across multiple transcriptomic datasets, helping to elucidate sex differences in numerous diseases. Its use will facilitate the generation of novel biological knowledge that can be used in the research and application of Personalized Medicine considering the sex of patients.

Septal Defects: Unveiling Sex-Based Disparities and Screening Challenges for Timely Intervention Through a Case Report and Systematic Literature Review.

Atrial septal defects (ASDs), comprising a significant portion of congenital cardiac anomalies, encompass a rarer and more diagnostically challenging subset known as sinus venosus ASDs (SVASDs). ASDs are more prevalent in females, and the prognosis for patients under 40 years of age is generally favorable with advancements in surgical and transcatheter interventions. However, undiagnosed ASDs in adults above 40 years old, especially females, often lead to severe complications, including pulmonary hypertension, atrial fibrillation, Eisenmenger syndrome, and a mortality rate exceeding 50%. Our detailed case study focuses on an obese 42-year-old Hispanic migrant female with chronic respiratory failure misattributed to pulmonary hypertension, resulting in the progression of complications from undiagnosed SVASD. Further investigation using contrast-enhanced transesophageal echocardiography (TEE) elucidated the correct diagnosis four years after her initial presentation. This report explores the potential factors contributing to the patient's delayed diagnosis and development of advanced cardiac complications of pulmonary hypertension leading to Eisenmenger syndrome that precluded her from procedural intervention. Furthermore, this report pioneers the first thorough review of case reports in adults newly diagnosed with SVASD, revealing sex-based differences in complications.

Chemoreflex sensitization occurs in both male and female rats during recovery from acute lung injury.

Introduction: Sex-specific patterns in respiratory conditions, such as asthma, COPD, cystic fibrosis, obstructive sleep apnea, and idiopathic pulmonary fibrosis, have been previously documented. Animal models of acute lung injury (ALI) have offered insights into sex differences, with male mice exhibiting distinct lung edema and vascular leakage compared to female mice. Our lab has provided evidence that the chemoreflex is sensitized in male rats during the recovery from bleomycin-induced ALI, but whether sex-based chemoreflex changes occur post-ALI is not known. To bridge this gap, the current study employed the bleomycin-induced ALI animal model to investigate sex-based differences in chemoreflex activation during the recovery from ALI. Methods: ALI was induced using a single intra-tracheal instillation of bleomycin (bleo, 2.5 mg/Kg) (day 1). Resting respiratory frequency (fR) was measured at 1-2 days pre-bleo, day 7 (D7) post-bleo, and 1 month (1 mth) post-bleo. The chemoreflex responses to hypoxia (10% O2, 0% CO2) and normoxic-hypercapnia (21% O2, 5% CO2) were measured before bleo administration (pre-bleo) and 1 mth post-bleo using whole-body plethysmography. The apnea-hypopnea Index (AHI), post-sigh apneas, and sighs were measured at each time point. Results: There were no significant differences in resting fR between male and female rats at the pre-bleo time point or in the increase in resting fR at D7 post-bleo. At 1 mth post-bleo, the resting fR was partially restored in both sexes but the recovery towards normal ranges of resting fR was significantly lower in male rats. The AHI, post-sigh apneas, and sighs were not different between male and female rats pre-bleo and 1 mth post-bleo. However, at D7 post-bleo, the male rats exhibited a higher AHI than female rats. Both male and female rats exhibited a sensitized chemoreflex in response to hypoxia and normoxic-hypercapnia with no significant differences between sexes. Conclusion: A sex difference in resting ventilatory parameters occurs post ALI with a prolonged increase in resting fR and larger AHI in male rats. On the other hand, we did not find any sex differences in the chemoreflex sensitization that occurs at 1 mth post-bleo. This work contributes to a better understanding of sex-based variations in lung disorders.

Regional variation in bone mineral density of the distal radius.

Objectives: This study investigates the regional variation in areal bone mineral density (aBMD) at the distal radius, a critical site for osteoporosis-related fractures. Understanding aBMD distribution is essential for accurate diagnosis and management of osteoporosis. Methods: The study involved 261 participants aged over 50. Using dual-energy X-ray absorptiometry (DXA) scans, aBMD was recorded across contiguous regions of the distal radius. Factors considered include age, sex, and hand dominance, providing a comprehensive view of aBMD distribution. Results: The findings indicated a consistent pattern in aBMD distribution along the radius, with a plateau around the one-third distance from the wrist. Notably, significant differences in aBMD were observed between age groups, especially among post-menopausal women. The study also recorded minor variations in aBMD between dominant and non-dominant forearms. Conclusions: The study's insights into aBMD variation at the distal radius have implications for osteoporosis research and clinical diagnosis. It highlights the importance of standardized region of interest placement in DXA scans for accurate assessment.

The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies.

BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions. METHODS: We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors. RESULTS: We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles. CONCLUSIONS: Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.

Schizophrenia is a serious illness characterised by changes in perception, mood and behaviour that profoundly affect patients and society. The frequency, symptoms and progression of schizophrenia are different in women and men, but the biological reason for this is not understood. The identification of disease mechanisms specific in men and women, is relevant because it would allow a better understanding of this pathology, as well as improving the personalisation of diagnoses and treatments for patients. To achieve this goal, in this work we reviewed all available RNA sequencing studies of post-mortem brain samples from women and men affected by schizophrenia. Then, we compared gene expression in each study by sex, and integrated all study results in different brain regions: prefrontal cortex, hippocampus and all-studies. We discovered significant changes between men and women: 265 genes differentially expressed in the prefrontal cortex, 1414 genes in the hippocampus and 66 genes in meta-analyses of all-studies. The study of these genes revealed increased immune response functions in the prefrontal cortex of men and in the hippocampus of women with schizophrenia, as well as increased neurotransmission and synapses in the prefrontal cortex of women with schizophrenia. Our results report multiple gene expression changes in specific brain regions of patients with schizophrenia, providing new insights into the role of sex in schizophrenia.

Association Between Female Sex and Better Survival in Gastroenteropancreatic Neuroendocrine Tumors.

INTRODUCTION: Studies conflict on whether sex influences survival in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). GEP-NETs express receptors and genes responsive to female hormones. We hypothesized that women would have improved survival and this difference would be greater in premenopausal age women compared to older women. MATERIALS AND METHODS: The National Cancer Database from 2004 to 2016 was queried for patients with GEP-NETs based on histologic code. Demographic, tumor, treatment, and socioeconomic characteristics were compared between men and women and age ≤45 or >65 y using Fisher's exact and Wilcoxon tests as appropriate. The primary endpoint was overall survival (OS), assessed by Kaplan-Meier survival analysis. RESULTS: Included in the study were 73,521 patients with small bowel neuroendocrine tumors (SBNETs), gastric neuroendocrine tumors (GNETs), or pancreas neuroendocrine tumors (36,197 female, 37,324 male). Women lived longer regardless of primary site, with the largest difference in GNETs (median OS 139 versus 85 mo) and smallest in SBNETs (121 versus 116, P < 0.001 for both). While male patients more often had high grade and metastatic disease, female sex remained independently associated with improved OS after adjusting for confounders (hazard ratio 0.84, P < 0.001). In GNETs and SBNETs, female sex had a larger beneficial effect on OS in premenopausal than postmenopausal patients. CONCLUSIONS: Women with GEP-NETs have improved survival over men, especially in the premenopausal age group. This may be due to a protective effect of female hormones; however, further studies are necessary to uncover the biologic basis of this difference.

Sex Differences in Coronary Artery Disease Characteristics Among Patients With Type 2 Myocardial Infarction.

Background: Type 2 myocardial infarction (MI) results from coronary supply and demand imbalance and has a poor prognosis. It is crucial to identify potential sex-based differences in the prevalence and nature of coronary artery disease (CAD) within this population. Objectives: The purpose of this study was to evaluate sex-based disease differences in type 2 MI among patients evaluated with coronary computed tomography angiography and fractional flow reserve. Methods: In a single-center, prospective study, patients with strictly adjudicated type 2 MI underwent coronary computed tomography angiography with fractional flow reserve. Results: Among 50 study participants enrolled, 50% were women. A similar mix of MI precipitants was present in both sexes. ST-segment depression was more common in women (64% vs 32%), while men were more likely to have T wave inversion (68% vs 36%). Women and men had comparable coronary artery calcium scores (median: 152 [Q1, Q3: 45, 762] vs 234 [Q1, Q3: 56, 422]). Prevalence of any CAD (84% vs 100%), obstructive CAD (24% vs 28%), and hemodynamically significant focal stenosis (20% vs 32%) were similar between sexes. Total plaque volume was similar between sexes, but women had significantly lower levels of low-attenuation plaque (median: 3 [Q1, Q3: 1, 7] vs 9 [Q1, Q3: 3, 14]). Conclusions: Among patients with type 2 MI, prevalence of any CAD and obstructive CAD did not differ according to sex. Total plaque volume was similar between sexes, but women had a lower volume of low-attenuation plaque (DEFINing the PrEvalence and Characteristics of Coronary Artery Disease Among Patients With TYPE 2 Myocardial Infarction Using CT-FFR [DEFINE TYPE2MI]; NCT04864119).

Gender Differences in the Cortical Distribution of Corpus Callosum Fibers.

Introduction Research on gender-based disparities in human brain structure has spanned over a century, yielding conflicting results and ongoing debate. While some studies indicate minimal distinctions, others consistently highlight differences in the corpus callosum (CC), even after accounting for average brain size. Methods Diverging from previous approaches, this study examines the morphology of the entire CC fiber rather than solely focusing on its midsagittal structure. Utilizing advanced neuroimaging techniques and generalized Q-imaging tractography, CC streamlines were constructed to assess gender differences in fractional anisotropy (FA), volume ratio, and cortical distribution. Student's t-test was employed to examine the disparities in FA between gender groups, while gender-based distinctions in the normalized volume of the CC and its segments were assessed using analysis of covariance (ANCOVA), with absolute whole white matter volume serving as a covariate. Results No significant gender-based disparities were found in either FA or normalized CC volume. While females exhibited consistently larger normalized volume CC streamlines than males, these differences lost statistical significance after adjusting for absolute total white matter volume as a covariate. Nonetheless, CC streamlines in females displayed a broader spatial distribution, encompassing various cortical regions, including the bilateral prefrontal cortex (medial and lateral surfaces), as well as medial parietal and temporal regions. Conclusion This study elucidates gender-related variations in the morphology of the brain's white matter pathways, indicating a more widespread cortical distribution of CC fibers in females compared to males. However, the study underscores the need for further investigations into connectivity patterns to fully elucidate these gender-based disparities.

Rates of pulmonary vein reconnection at repeat ablation for recurrent atrial fibrillation and its impact on outcomes among females and males.

BACKGROUND: Several studies have demonstrated that females have a higher risk of arrhythmia recurrence after pulmonary vein (PV) isolation for atrial fibrillation (AF). There are limited data on sex-based differences in PV reconnection rates at repeat ablation. We aimed to investigate sex-based differences in electrophysiological findings and atrial arrhythmia recurrence after repeat AF ablation METHODS: We conducted a retrospective study of 161 consecutive patients (32% female, age 65 ± 10 years) who underwent repeat AF ablation after index PV isolation between 2010 and 2022. Demographics, procedural characteristics and follow-up data were collected. Recurrent atrial tachycardia (AT)/AF was defined as any atrial arrhythmia ≥30 s in duration. RESULTS: Compared to males, females tended to be older and had a significantly higher prevalence of prior valve surgery (10 vs. 2%; P = .03). At repeat ablation, PV reconnection was found in 119 (74%) patients. Males were more likely to have PV reconnection at repeat ablation compared to females (81 vs. 59%; P = .004). Excluding repeat PV isolation, there were no significant differences in adjunctive ablation strategies performed at repeat ablation between females and males. During follow-up, there were no significant differences in freedom from AT/AF recurrence between females and males after repeat ablation (63 vs. 59% at 2 years, respectively; P = .48). CONCLUSIONS: After initial PV isolation, significantly fewer females have evidence of PV reconnection at the time of repeat ablation for recurrent AF. Despite this difference, long-term freedom from AT/AF was similar between females and males after repeat ablation.

Greater glycemic control following low-load, high-repetition resistance exercise compared with moderate-intensity continuous exercise in males and females: a randomized control trial.

Exercise has long been known for its beneficial effects on insulin sensitivity (IS) and glucose handling with both moderate-intensity continuous (MIC) exercise and resistance exercise (RE) inducing beneficial effects. In recent years, low-load, high-repetition (LLHR) RE has emerged as a strategy to increase muscle mass and strength to levels similar to traditional RE; however, the effects of LLHR RE on glucose handling has yet to be investigated. The purpose of this trial was to compare the acute effects of LLHR RE to MIC exercise on post-exercise glycemic control and insulin sensitivity in males and females. Twenty-four (n = 12/sex) participants completed acute bouts of MIC exercise (30 min at 65% V̇O2peak) and LLHR (3 circuits, 6 exercises/circuit, 25-35 repetitions/exercise/circuit) matched for time with muscle biopsies immediately pre and post exercise and an oral glucose tolerance test (OGTT) 90 min following exercise. Blood glucose concentrations (p = 0.002, ηp 2 = 0.37), glucose AUC (p = 0.002, ηp 2 = 0.35) and max glucose concentration (p = 0.003, ηp 2 = 0.34) were lower during the post exercise OGTT following LLHR RE compared to MIC exercise. There was a main effect of trial on TBC1D1 Ser237 phosphorylation (p = 0.04, ηp 2 = 0.19) such that it was greater following MIC exercise compared to LLHR RE. Furthermore, phosphorylated ACC Ser79 increased following MIC exercise with no change following LLHR RE (p < 0.001, ηp 2 = 0.50). Phosphorylation of PTEN Ser380 was greater in males than females during LLHR RE (p = 0.01, ηp 2 = 0.27). These findings suggest that LLHR RE is a feasible exercise modality to improve post-exercise glycemic control in both males and females. Trial registration number: NCT06217679.

Sex Differences in Quadriceps Atrophy After Anterior Cruciate Ligament Tear.

BACKGROUND: Female athletes lag behind their male counterparts in recovery from anterior cruciate ligament (ACL) injury. Quadriceps muscle size and strength are crucial factors for regaining function after ACL injury, but little is known about how these metrics vary due to biological sex. HYPOTHESIS: Female patients have reduced vastus lateralis fiber cross-sectional area (CSA) and lower quadriceps strength after ACL injury than male patients. STUDY DESIGN: Cross-sectional study. LEVEL OF EVIDENCE: Level 4. METHODS: A total of 60 participants with recent ACL tear were evaluated for vastus lateralis muscle fiber CSA, isometric quadriceps peak torque, and quadriceps rate of torque development. Linear mixed models were fit to determine differences across sex and limb for each variable of interest. RESULTS: The female group averaged almost 20% atrophy between limbs (P < 0.01), while the male group averaged just under 4% (P = 0.05). Strength deficits between limbs were comparable between female and male groups. CONCLUSION: Immediately after ACL injury, female patients have greater between-limb differences in muscle fiber CSA but between-limb strength deficits comparable with those of male patients. CLINICAL RELEVANCE: These results indicate that the underpinnings of strength loss differ based on biological sex, and thus individual patients could benefit from a sex-specific treatment approach to ACL injury.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults.

INTRODUCTION: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. METHODS: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. RESULTS: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24-3.56) and 0.45 per 100 person-years (95% CI: 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62-4.84) and 0.75 per 100 person-years (95% CI: 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56-3.16) and 0.21 per 100 person-years (95% CI: 0.067-0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). CONCLUSION: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

Novel insight into the lipid network of plasma extracellular vesicles reveal sex-based differences in the lipidomic profile of alcohol use disorder patients.

BACKGROUND: Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. METHODS: We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX2, which evaluates enzymatic dysregulation using an enrichment algorithm. RESULTS: Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with "negative intrinsic curvature" and "positive intrinsic curvature", respectively. CONCLUSIONS: Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.

Alcohol use disorder (AUD) is one of the most common psychiatric disorders, with the consumption of alcohol considered a leading cause of preventable deaths worldwide. Lipids play a crucial functional role in cell membranes; however, we know little about the role of lipids in extracellular vesicles (EVs) as regulatory molecules and disease biomarkers. We employed a sensitive lipidomic strategy to characterize lipid species from the plasma EVs of AUD patients to evaluate functional roles and enzymatic activity networks to improve the knowledge of lipid metabolism after alcohol consumption. We analyzed plasma EV lipids from AUD females and males and healthy individuals to highlight lipids with differential abundance and biologically interpreted lipidomics data using LINEX², which evaluates enzymatic dysregulation using an enrichment algorithm. Our results show, for the first time, that AUD females exhibited more significant substrate-product changes in lysophosphatidylcholine/phosphatidylcholine lipids and phospholipase/acyltransferase activity, which are potentially linked to cancer progression and neuroinflammation. Conversely, AUD males suffer from dysregulated ceramide and sphingomyelin lipids involving sphingomyelinase, sphingomyelin phosphodiesterase, and sphingomyelin synthase activity, which relates to hepatotoxicity. Notably, the analysis of plasma EVs from AUD females and males demonstrates enrichment of lipid ontology terms associated with "negative intrinsic curvature" and "positive intrinsic curvature", respectively. Our methodological developments support an improved understanding of lipid metabolism and regulatory mechanisms, which contribute to the identification of novel lipid targets and the discovery of sex-specific clinical biomarkers in AUD.

Sex-based differences in ischemic cardiovascular and bleeding outcomes following implantation of drug-eluting stent in patients at high bleeding risk.

BACKGROUND: Patients with high bleeding risk (HBR) may exhibit uncertain adherence to dual antiplatelet therapy (DAPT) following drug-eluting stent (DES) implantation. The current population-based cohort study aimed to investigate the sex-based differences in adverse outcomes among the HBR population by analyzing the National Health Insurance Research Database in Taiwan. METHODS: Patients who had HBR features defined by the Academic Research Consortium (ARC) and received DES implantation between January 1, 2007, and December 31, 2017, were enrolled. Propensity score matching was adopted to select 3,981 pairs with similar clinical cardiovascular risks but different sexes. A competing risk model was performed to evaluate the risk of adverse ischemic events (cardiac death, nonfatal myocardial infarction, and ischemic stroke) and any bleeding events in both sexes. Noncardiac death was considered a competing risk. RESULTS: Within a 5-year follow-up, the incidence rates (per 1,000 person-year (95% confidence interval (CI)) of composite ischemic events and any bleeding events in males were respectively 44.09 (40.25-48.30) and 42.55 (38.79-46.68), while those in females were respectively 40.18 (36.51-44.23) and 42.35 (38.57-46.51). After adjustment for clinical variables, male patients had a marginally increased risk in the composite ischemic events (adjusted subdistribution hazard ratio (SHR) = 1.15 (1.00-1.31), p = 0.045) and a similar risk of any bleeding events (adjusted SHR = 1.00 (0.88-1.15), p = 0.946) compared with female patients. CONCLUSIONS: Of the HBR population, males had an increased risk of ischemic outcomes but a similar risk of bleeding compared with females following DES implantation.

The role of microRNAs in understanding sex-based differences in Alzheimer's disease.

BACKGROUND: The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment. METHODS: A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms. RESULTS: Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process. CONCLUSIONS: Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.

Alzheimer's disease (AD)­a neurodegenerative disease mainly affecting older patients­is characterized by cognitive deterioration, memory loss, and progressive incapacitation in daily activities. While AD affects almost twice as many females as males, and cognitive deterioration and brain atrophy develop more rapidly in females, the biological causes of these differences remain poorly understood. MicroRNAs (miRNAs) regulate gene expression and impact a wide variety of biological processes; therefore, studying the differential expression of miRNAs in female and male AD patients could contribute to a better understanding of the disease. We reviewed studies of miRNA expression in female and male AD patients and integrated results using a meta-analysis methodology and then identified those genes regulated by the altered miRNAs to establish an association with biological processes. We found 16 (females) and 22 (males) miRNAs altered in the blood of AD patients. Functional enrichment revealed sex-based differences in the affected altered biological processes­protein modification and degradation and cell death in male AD patients and RNA processing in female AD patients. A similar analysis in the brains of AD patients revealed six (females) and four (males) miRNAs with altered expression; however, our analysis failed to highlight any specifically altered biological processes. Overall, we highlight the sex-based differential expression of miRNAs (and biological processes affected) in the blood and brain of AD patients.

Nuclear-localized androgen receptor content following resistance exercise training is associated with hypertrophy in males but not females.

Androgen receptor (AR) content has been implicated in the differential response between high and low responders following resistance exercise training (RET). However, the influence of AR expression on acute skeletal muscle damage and whether it may influence the adaptive response to RET in females is poorly understood. Thus, the purpose of this exploratory examination was to 1) investigate changes in AR content during skeletal muscle repair and 2) characterize AR-mediated sex-based differences following RET. A skeletal muscle biopsy from the vastus lateralis was obtained from 26 healthy young men (n = 13) and women (n = 13) at baseline and following 300 eccentric kicks. Subsequently, participants performed 10 weeks of full-body RET and a final muscle biopsy was collected. In the untrained state, AR mRNA expression was associated with paired box protein-7 (PAX7) mRNA in males. For the first time in human skeletal muscle, we quantified AR content in the myofiber and localized to the nucleus where AR has been shown to trigger cellular outcomes related to growth. Upon eccentric damage, nuclear-associated AR (nAR) content increased (p < .05) in males and not females. Males with the greatest increase in cross-sectional area (CSA) post-RET had more (p < .05) nAR content than females with the greatest gain CSA. Collectively, skeletal muscle damage and RET increased AR protein, and both gene and hypertrophy measures revealed sex differences in relation to AR. These findings suggest that AR content but more importantly, nuclear localization, is a factor that differentiates RET-induced hypertrophy between males and females.

Sex-based outcomes in surgical repair of acute type A aortic dissection: A meta-analysis and meta-regression.

OBJECTIVE: Epidemiologic variation with respect to sex has been established in aortic dissection. However, current literature on sex-based outcomes in patients with aortic dissection is conflicting. In this study we aimed to compare perioperative outcomes according to sex in patients treated surgically for acute type A aortic dissection. METHODS: PubMed/MEDLINE, Embase, and Web of Science were searched for studies that reported sex-based differences in postoperative outcomes among patients with acute type A aortic dissection. The primary outcome was in-hospital/30-day mortality, and secondary outcomes included postoperative stroke, renal failure requiring dialysis, and reoperation for bleeding. Data were aggregated using the random effects model as pooled risk ratio (RR). Meta-regression was applied to identify sources of heterogeneity between studies. RESULTS: Nine of 1022 studies were included for final analysis comprising 3338 female and 5979 male participants. Compared with male sex, female sex was associated with similar in-hospital/30-day mortality (RR, 1.04; 95% CI, 0.85-1.28; P = .67), postoperative stroke risk (RR, 1.07; 95% CI, 0.91-1.25; P = .43), and postoperative risk of acute renal failure requiring dialysis (RR, 0.84; 95% CI, 0.59-1.19; P = .32). A decreased risk of reoperation for bleeding (RR, 0.84; 95% CI, 0.75-0.94; P < .01) was observed in female participants. Meta-regression analysis indicated that differences in preoperative shock were a source of heterogeneity in the sex difference in in-hospital/30-day mortality across studies. CONCLUSIONS: Among patients treated surgically for acute type A aortic dissection, female sex was not associated with increased risk of short-term mortality nor with major postoperative complications. Male sex was associated with a greater risk of postoperative bleeding.